RESUMEN
BACKGROUND: Esophageal cancer (EC) is one of the most aggressive malignant gastrointestinal tumors; however the traditional therapies for EC are not effective enough. Great improvements are needed to explore new and valid treatments for EC. We aimed to screen the differentially expressed miRNAs (DEMs) in esophageal cancer and explore the pathogenesis of esophageal cancer along with functions and pathways of the target genes. MATERIAL AND METHODS: miRNA high-throughput sequencing data were downloaded from The Cancer Genome Atlas (TCGA), then the DEMs underwent principal component analysis (PCA) based on their expression value. Following that, TargetScan software was used to predict the target genes, and enrichment analysis and pathway annotation of these target genes were done by DAVID and KEGG, respectively. Finally, survival analysis between the DEMs and patient survival time was done, and the miRNAs with prediction potential were identified. RESULTS: A total of 140 DEMs were obtained, 113 miRNAs were up-regulated including hsa-mir-153-2, hsa-mir-92a-1 and hsa-mir-182; while 27 miRNAs were down-regulated including hsa-mir comprising 29a, hsa-mir-100 and hsa-mir-139 and so on. Five miRNAs (hsa-mir-103-1, hsa-mir-18a, hsa-mir-324, hsa-mir-369 and hsa-mir-320b-2) with diagnostic and preventive potential were significantly correlated with survival time. CONCLUSIONS: The crucial molecular targets such as p53 may provide great clinical value in treatment, as well to provide new ideas for esophageal cancer therapy. The target genes of miRNA were found to play key roles in protein phosphorylation, and the functions of the target genes during protein phosphorylation should be further studied to explore novel treatment of EC.
Asunto(s)
Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Anciano , Biología Computacional , Neoplasias Esofágicas/mortalidad , Femenino , Perfilación de la Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , Análisis de Componente Principal , Modelos de Riesgos Proporcionales , Programas Informáticos , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
The objective of this study was performed to investigate the effects of thapsigargin on apoptosis, actin cytoskeletal dynamics, and actin cytoskeletal proteins in human lung adenocarcinoma cell. Thapsigargin is a specific irreversible inhibitor of ER calcium-ATPase, which may promote ER stress by depletion of lumenal calcium stores and show potential to induce cell death. The effects of thapsigargin on the apoptosis in A549 cells were assayed by Hoechst staining. Moreover, the F-actin staining by Rhodamine-phalloidin and RhoA antibody for cytoskeleton organizations were applied to A549 cells. To confirm the impairment of cytoskeletal dynamics treated with thapsigargin, western blots were applied to analyze the protein levels of p-Cofilin-1 (Ser3), Cofilin-1, and pPaxillin (Tyr118), as well as RhoA and pS6 (S240/244). Results suggest that thapsigargin may induce cell death in A549 cells with a time- and dose-dependent manner. The F-actin fibers and RhoA signals are also reduced with a time- and dose-dependent manner by thapsigargin treatment. The phosphorylation forms of Cofilin-1 and paxillin are attenuated by 1 µM thapsigargin treatment for 24 h. These alternations may be caused by the inhibition of of mTORC1 activities (indicated by pS6 (Ser240/244)) and RhoA pathways after thapsigargin treatment. The present findings highlight important roles of calcium entry in cytoskeleton organization and apoptosis in human lung adenocarcinoma cells and will help to set a stage to the clinical treatment of cancer cell metastasis.
Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Proteínas del Citoesqueleto/metabolismo , Citoesqueleto/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Tapsigargina/farmacología , Western Blotting , Calcio/metabolismo , ATPasas Transportadoras de Calcio/antagonistas & inhibidores , Línea Celular Tumoral , Cofilina 1/metabolismo , Citoesqueleto/fisiología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Paxillin/metabolismoRESUMEN
BACKGROUND: The fall armyworm (FAW) Spodoptera frugiperda Smith (Lepidoptera: Noctuidae) invaded Myanmar and China in 2018 and greatly impacted agricultural production and ecosystem balance in these areas. FAW is a migratory insect, but its seasonal migration pattern between the two countries has been largely unknown. From 2019 to 2021, we monitored the seasonal migration of FAW in the China-Myanmar border area using a searchlight trap, assessed the reproductive development status of female migrants and traced the migratory routes by trajectory simulation. RESULTS: FAW moths were trapped by the searchlight trap in Lancang County (Yunnan, China) all year, with obvious seasonal differences in the number caught. There were small-scale persistent trapping peaks in spring and summer, and obvious peaks in autumn; only a small number of moths were trapped in winter. Examination of the ovaries of female moths collected in different seasons showed that most females had matured, indicating that the moths were migrating and did not take off from the local area. In the migration trajectory simulation, FAW mainly migrated from Myanmar to Southwest China in spring and summer and back to Myanmar in autumn. CONCLUSION: Our findings indicate that FAW migrates between China and Myanmar according to the monsoon circulation, which will help guide cross-border regional monitoring and management strategies against this pest. © 2022 Society of Chemical Industry.
Asunto(s)
Ecosistema , Animales , China , Femenino , Mianmar , Estaciones del Año , SpodopteraRESUMEN
OBJECTIVE: To evaluate the possible role of alkaloid sinomenine (SIN) on chronic rejection in rat heart transplantation model. METHODS: After a brief course of cyclosporine A (CsA), DA recipients of PVG hearts were treated with placebo, SIN, CsA, or a combination of both drugs. Grafts were analyzed morphometrically and by immuno-histochemistry. Expressions of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and endothelin 1 (ET-1) were assessed by reverse transcription-polymerase chain reaction. RESULTS: Cardiac grafts of SIN-treated rats showed a mild degree of vasculopathy compared with untreated rats or CsA-treated recipients. Degree of vasculopathy was significantly reduced in rats treated with combined SIN and CsA than rats receiving either drug alone. Treatment with SIN alone did not affect gene expressions of bFGF, VEGF, and ET-1 while expressions of bFGF, VEGF, and ET-1 were significantly reduced by combined treatment with SIN and CsA. CONCLUSION: These results demonstrated a potential value of SIN, in combination with low-dose CsA to attenuate the vasculopathy in this rat model of chronic cardiac allograft rejection.
Asunto(s)
Rechazo de Injerto/tratamiento farmacológico , Trasplante de Corazón , Morfinanos/uso terapéutico , Fitoterapia , Animales , Modelos Animales de Enfermedad , Supervivencia de Injerto , Masculino , RatasRESUMEN
The present study aimed to identify the feature genes associated with smoking in lung adenocarcinoma (LAC) samples and explore the underlying mechanism. Three gene expression datasets of LAC samples were downloaded from the Gene Expression Omnibus database through preset criteria and the expression data were processed using metaanalysis. Differentially expressed genes (DEGs) between LAC samples of smokers and nonsmokers were identified using limma package in R. The classification accuracy of selected DEGs were visualized using hierarchical clustering analysis in R language. A proteinprotein interaction (PPI) network was constructed using gene interaction data from the Human Protein Reference Database for the DEGs. Betweenness centrality was calculated for each node in the network and genes with the greatest BC values were utilized for the construction of the support vector machine (SVM) classifier. The dataset GSE43458 was used as the training dataset for the construction and the other datasets (GSE12667 and GSE10072) were used as the validation datasets. The classification accuracy of the classifier was tested using sensitivity, specificity, positive predictive value, negative predictive value and area under curve parameters with the pROC package in R language. The feature genes in the SVM classifier were subjected to pathway enrichment analysis using Fisher's exact test. A total of 347 genes were identified to be differentially expressed between samples of smokers and nonsmokers. The PPI network of DEGs were comprised of 202 nodes and 300 edges. An SVM classifier comprised of 26 feature genes was constructed to distinguish between different LAC samples, with prediction accuracies for the GSE43458, GSE12667 and GSE10072 datasets of 100, 100 and 94.83%, respectively. Furthermore, the 26 feature genes that were significantly enriched in 9 overrepresented biological pathways, including extracellular matrixreceptor interaction, proteoglycans in cancer, cell adhesion molecules, p53 signaling pathway, microRNAs in cancer and apoptosis, were identified to be smokingrelated genes in LAC. In conclusion, an SVM classifier with a high prediction accuracy for smoking and nonsmoking samples was obtained. The genes in the classifier may likely be the potential feature genes associated with the development of patients with LAC who smoke.